Lecture 26

• Chapters


  • 8
  • 18
• Lab report 1 due April 12
• Homework re-dos due April 10
• Learning objectives


  • Describe the different types of aneuploidy and their effects in humans
  • Describe the different types of polyploidy and its role in evolution
  • Describe the different pathways of DNA repair
  • Types of chromosome mutations
  • Chromosome rearrangement
  • Aneuploidy
  • Polyploidy

  
• Types of chromosome mutations

  • Chromosome rearrangement
  • Aneuploidy
  • Polyploidy

  
• Paracentric inversions


  Recombinant chromosomes will be acentric or dicentric and have deletions and duplications

  
• Pericentric inversions


  Recombinant chromosomes will have normal centromeres, but still have deletions and duplications

  
• Robertsonian translocations


  Reciprocal translocation between two acrocentric chromosomes at their centromeres, generates one large metacentric chromosome and one tiny metacentric chromosome (usually lost)

  
• Aneuploidy


  The gain or loss of an entire chromosome

  
• Terms (in relation to a chromosome in a diploid, 2n)


  • Nullisomy = no copies of a particular chromosome (2n - 2)
  • Monosomy = one copy of a chromosome (2n - 1)
  • Trisomy = three copies of a chromosome (2n + 1)
  • Tetrasomy = four copies of a chromosome (2n + 2)

  
• Humans have a 2n = _______
• A person with a nullisomy has ________ chromosomes

  
• A person with a monosomy has ________ chromosomes

  
• A person with a trisomy has _________ chromosomes

  
• A person with a tetrasomy has ________ chromosomes
• Nondisjunction


  Failure of homologous chromosomes or sister chromatids to separate during meiosis or mitosis

  
• Both trisomy and monosomy cause gene dosage effects
• Monosomy also causes pseudodominant and haploinsufficiency effects
• Down syndrome is a result of trisomy 21
• Other trisomies arise, but do not survive to term
• Sex chromosome aneuploidy appears more common than autosomal aneuploidy

  
• Most aneuploidy is not tolerated in animals
• Patau syndrome (trisomy 13) causes severe developmental defects and 90% mortality in the first year
• Dosage compensation


  A mechanism to equalize the amount of protein produced by X-linked genes in males and females
• 1. chromosome inactivation


  Mammals use this to normalize gene dosage differences between males and females

  
• In XY males, the single X chromosome is unaffected

  
• In XX females, one X chromosome is inactivated during embryogenesis

  
• One X chromosome is randomly inactivated in each cell early in development

  
• 1. inactivation is state is inherited through mitosis causing females to be mosaics of clonal patches of cells expressing either the paternal or the maternal X chromosome

  
• 1. inactivation center (XIC)


  Contains the Xist gene

  
• Xist RNA


  Transcribed from one X chromosome, associates with the chromosome that expresses it and shuts off expression of ~85% of X-linked genes

  
• Sex chromosome aneuploidy is better tolerated than autosomal aneuploidy due to dosage compensation via X-chromosome inactivation

  
• A few genes remain active on the inactivated X, and these genes have an impact on development

  
• Turner syndrome


  45,X females

  
• Kleinfelter syndrome


  47,XXY males
• Down syndrome


  Trisomy 21, most common aneuploidy in humans, characterized by variable degrees of intellectual disability, slower growth and development, increased incidence of heart defects, leukemia, and other abnormalities
• 92% of those who have Down syndrome have 3 full copies of chromosome 21, called primary Down syndrome

  
• Often the result of nondisjunction during meiosis 1 in the maternal gametes
• Robertsonian translocation


  Translocation in which the long arm of two acrocentric chromosomes become joined to a common centromere, increases risk of Down syndrome in some families

  
• Polyploidy


  Extra copies of entire haploid sets of chromosomes